Integrin- and cadherin-mediated induction of the matrix metalloprotease matrilysin in clocultures of malignant oral squamous cell carcinoma cells anddermal fibroblasts

Matrilysin is a matrix metalloprotease (MMP) overexpressed in a number of c ancers including skin, head and neck squamous cell carcinomas, and prostate and colon adenocarcinomas. Matrilysin has been shown to play a role in the degradation of the basement membrane that separates epithelium from stroma allowing tumor cells to intravasate into the bloodstream and metastasize. Here, we show that an oral squamous cell carcinoma cell line (SCC-25) expre sses low levels of promatrilysin when cultured alone. However, when SCC-25 cells are cocultured with human foreskin fibroblasts (HFF), there is a 40-f old induction of promatrilysin expression. We tested whether this induction of promatrilysin expression was due to the release of paracrine factors, c ell-cell interactions, or cell-matrix interactions. Our results indicate in duced promatrilysin expression is the result of both cell-cell and cell-mat rix interactions. We demonstrate that beta1 integrins as well as cadherins, specifically N-cadherin and E-cadherin, are involved in the induction of p romatrilysin expression. Our results are of general interest in relation to the regulation of NMP expression through cell surface receptor regulation. Further investigation may lead to the identification of novel targets for suppression of invasion and metastasis in oral tumors. (C) 2001 Academic Pr ess.